4-Methylmorpholine → N-(cyanomethyl)-2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide

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Reaction Steps

2-Hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetic acid (Int-Va, 35 mg, 0.081 mmol) was dissolved in DMF (1 mL) prior to the addition of 4-methylmorpholine (0.054 mL, 0.487 mmol), 2-aminoacetonitrile, HCl (15.02 mg, 0.162 mmol), and HATU (61.7 mg, 0.162 mmol). This was stirred overnight and was then purified by preparative HPLC (PHENOMENEX® Luna 5u C18 21.2×100 mm, gradient elution with Method 1—MeOH/water containing 0.1% trifluoroacetic acid as defined above, 0% B to 100% B over 10 min, 20 mL/min, 220 nM, product retention time=33.2 min) to give single enantiomer N-(cyanomethyl)-2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide (18.3 mg, 0.038 mmol, 46.6% yield): LCMS=470.2 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.15-8.23 (2 H, m), 7.65-7.76 (4 H, m), 7.53-7.64 (3 H, m), 5.21 (1 H, s), 4.19 (2 H, d, J=2.86 Hz). HPLC Peak RT=9.5 min (Analytical Method A).

Provenance & Evidence